Evidence map›Paper›PMID 40450684›Full record

ArticleCell reports2025

Molecular basis of autoimmune disease protection by MDA5 variants.

Rahul Singh, Joe D Joiner, Alba Herrero Del Valle, Marleen Zwaagstra, Ida Jobe, Brian J Ferguson, Frank J M van Kuppeveld, Yorgo Modis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Establishing the molecular basis for MDA5 mutation-linked autoimmunity.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Rahul SinghMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Joe D JoinerMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.
Alba Herrero Del ValleMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK; Department of Genomes and Genetics, Institut Pasteur, 75724 Paris, France.
Marleen ZwaagstraSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, the Netherlands.
Ida JobeMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Brian J FergusonDepartment of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Frank J M van KuppeveldSection of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, the Netherlands.
Yorgo ModisMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address: ymodis@mrc-lmb.cam.ac.uk.

Funding

Wellcome Trust 101908Wellcome Trust 217191
6 · The paper itself

Abstract

MDA5 recognizes double-stranded RNA (dsRNA) from viruses and retroelements. Cooperative filament formation and ATP-dependent proofreading confer MDA5 with the necessary sensitivity and specificity for dsRNA. Many MDA5 genetic variants are associated with protection from autoimmune disease while increasing the risk of infection and chronic inflammation. How these variants affect RNA sensing remains unclear. Here, we determine the consequences of autoimmune-protective variants on the molecular structure and activities of MDA5. Rare variants E627

Indexed as

Autoimmune DiseasesInterferon-Induced Helicase, IFIH1Adenosine TriphosphateAnimalsCryoelectron MicroscopyHumansRNA, Double-StrandedAdenosine TriphosphateIFIH1 protein, humanInterferon-Induced Helicase, IFIH1RNA, Double-StrandedATPaseautoimmune disease mutationsCP: Immunologydouble-stranded RNA (dsRNA)fitness tradeoffhuman genetic variantsinnate immunitymolecular mechanism of diseaseRIG-I-like receptor (RLR)RNA helicaseRNA sensing

Identifiers

PMID40450684
PMCPMC7618376

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.